We have used a perifusion system to study the regulation of GH and Prl secretion by normal and neoplastic rate pituitary tissue. We have observed that normal rat pituitaries in this system respond to TRH and hypothalamic extract with increased GH secretion and to somatostatin with a blockage of GH secretion. In our system experimental rat pituitary tumors do not respond to hypophysiotropic hormones in the same manner as normal rat pituitaries. We postulate that rat pituitary tumors have a decreased concentration of receptors for TRH and somatostatin. We will use labeled TRH and somatostatin to measure these receptors directly. Our experiments indicate that the cessation of somatostatin perifusion is followed by a rapid over shoot of GH secretion suggesting to us that this agent blocks a terminal step in GH secretion. We hope to establish that such a mechanism exists by carefully adjusting the dose of somatostatin in the presence of theophylline so that GH secretion is blocked despite a great rise in cyclic AMP. We will continue our measurements of circulating GH by a radioreceptor assay in an attempt to recognize immuno-cross reactive but biologically inactive GH in certain cases of short stature and high GH. We plan a prospective study of the incidence of disturbances in prolactin secretion in cases of otherwise uncomplicated secondary amenorrhea. We plan a series of experiments to determine the GH receptor concentration in liver and other tissues. Exploratory studies will be conducted to detect GH receptors in readily available human tissues in an attempt to define the mechanism of certain types of GH refractoriness (Laron dwarfism). In collaboration with Dr. Mendelsohn of the Dept. of Psychiatry we will continue the study of GH release during sleep and its modification by pharmacologic agents. Studies of the properties of GH and prolactin secretory granules isolated from bovine pituitaries will be continued.